Biological tumor volume in ¹⁸ FET-PET before radiochemotherapy correlates with survival in GBM

Abstract

OBJECTIVE The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-l-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM). METHODS Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models. RESULTS Biological tumor volume before RCx (BTVpreRCx) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTVpreRCx had significantly longer progression-free and overall survival (OS). (18)FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS. CONCLUSION BTVpreRCx and TAC represent important (18)FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTVpreRCx is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection. Originally published at: Suchorska, B; Jansen, N L; Linn, J; Kretzschmar, H; Janssen, H; Eigenbrod, S; Simon, M; Pöpperl, G; Kreth, F W; la Fougere, C; Weller, M; Tonn, J C (2015). Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM. Neurology, 84 (7)

PET Imaging in Glioblastoma: Use in Clinical Practice

“…Thus, in addition to its value in biopsy planning, PET data provide added prognostic value with regard to surgical resection outcome (61). It has moreover been suggested that patients with glioblastomas may potentially benefit from maximal PET-guided tumor resection since lower biological tumor volume (BTV) before treatment with 18 F-FET was independent of clinical prognostic factors: patients with smaller tumor volumes had significantly longer progression-free and overall survival (62).…”

“…Indeed, 11 C-MET uptake is correlated to prognostic, histological, and molecular parameters in gliomas at initial stage (102). Moreover, a prospective multicenter trial investigating the role of pretreatment 18 F-FET PET in newly diagnosed glioblastoma found BTV prior to radiochemotherapy to be highly prognostic of outcome (62). Furthermore, 18 F-FET PET time-activity curves before treatment and their changes after radiochemotherapy were also related to outcome, whereby patients with increasing time-activity curves experienced longer overall survival (62).…”

“…Large BTC on 18 an independent prognostic factor of poor overall survival and of progression-free survival in newly diagnosed glioblastoma patients, to the detriment of other prognosis factors such as clinical factors or MRI-based tumor volume (62,68). A number of centers have accordingly begun to integrate amino acid imaging into CT-based and MRI-based radiotherapy planning (69), particularly in high-grade gliomas and in instances when high-precision radiotherapy is to be given, or in the setting of dose escalation studies, or for re-irradiation of recurrent tumors (70,71).…”

PET for Therapy Response Assessment in Glioblastoma

“…The biological tumor volume on 18 F-FET PET prior to chemoradiotherapy and as early as 7-10 days after the completion of treatment in GB was also found to be highly prognostic. Remarkably, the time-to-peak and the shape of the 18 F-FET time-activity curve, derived from dynamic PET acquisitions, were shown to have value in therapy response assessment (6,60,70,79,80).…”

“…Detection of this phenomenon in tumors is of utmost clinical relevance because tumor aggressiveness, metastatic spread, failure to achieve local tumor control, increased rate of recurrence, and ultimate poor outcome are all associated with hypoxia (39,102,103 (39,40,45,88). To date, 18 F-FMISO has predominantly been used in a preclinical setting (79,104). Concerning its use in therapy response assessment, the volume and intensity of hypoxia on 18 F-FMISO PET in GB before radiotherapy was strongly associated with poorer time to progression and survival (57).…”